1. Field of the Invention
The invention relates to novel compounds endowed with biological and pharmacological properties of great value, and notably among these products, those which show immune mechanism regulating properties.
The invention also relates to the applications of these novel products, to the compositions which are specially suitable for their application and to methods of treating animal or human hosts by administering these novel compounds.
2. Description of the Prior Art
As is known considerable efforts have been consacrated for a long time to research for agents endowed with immune reaction regulating properties. These researches have led first to the preparation of extracts of natural products notably of fragments of peptidoglycans from mycobacteria walls, then to synthetic molecules with relatively small molecules. Series of products with very interesting properties are thus available.
In the course of these researches, at the same time as these novel products novel properties have appeared, and in the same way, novel possibilities of utilization. In consequence, the necessity was felt of finding products responding better to the uses arising from the application of these novel properties, whether it relates to facilitating one or several types of activity to the maximum, whether it is desired to split the various possible activities to have available products with a very specific action, or again whether it is desired to reduce or eliminate certain undesirable side effects.
To arrive at these objectives, one is obliged to modify certain forms of administration, but above all researches have been undertaken to modify the activity of the compounds concerned by varying certain elements of their structure.
In previous work, certain authors have attempted to establish relationships between certain configurations or structural elements and the appearance of given properties, or again between various properties of this type of product. Thus Japanese researchers have observed, in a publication (SHOZO KOTANI AND COLL., Biken Journal, Vol. 19, 9-13, 1976), that there existed an apparent correlation between the immune adjuvant effect of these substances and the pyrogenic effect which can appear in certain experimental conditions, notably for the administration of high doses.
SHOZO KOTANI and coll. have offered the hypothesis that this pyrogenicity could possibly be attributed to the relationship between the compounds concerned and the fragments of peptidoglycans which can be obtained from gram-positive bacteria. Again in this publication, the authors assumed that there could exist a relationship between the mechanisms taking part in the immune responses under the effect of antigen stimulation and those taking part in the regulation of the temperature of the body or of the febrile response. They observe in fact that, among the compounds that they have tested, the most adjuvant are also the most pyrogenic.
The pyrogenic character of these substances can constitute a drawback which is not negligible. If this character is very marked, the administration of the substance can trigger, a dangerous phenomenon of thermal shock in the subject treated. In another connection, even when the pyrogenic character is slight or is only manifested at relatively high doses, it results nonetheless in limitations of use which may be troublesome. The doses used must be controlled rigorously, or again, certain methods of administration, in particular the intravenous route, must be avoided.
For these reasons, it is still important to have available novel substances of this type offering a widened choice of combinations of properties and thus enabling better adaptation of the contemplated use. It is in this sense, that the researches which resulted in the invention, were undertaken.
One improvement aimed at by the researches which led to the present invention was the increase in the activity of the compounds of this type for a particular dose, notably by attempting to reduce the speed of catabolism of the product by the organism of the host to whom it is administered. More particularly, an object of these researches was the synthesis of products more resistant to enzymatic hydrolysis.
Another object of the invention was to enable if necessary the establishment of novel pharmacological properties or combinations of properties, or again their increase to a level not hitherto obtained. With this in view, it was particularly desirable to have available products of which the therapeutic index, that is to say the ratio of the effective doses to the limiting doses for which undesirable phenomena commence to appear is as large as possible.
The desired improvements and modifications have been achieved, at least in part, by the products according to the present invention, notably in that adjuvant products are obtained which do not manifest any pyrogenic effect, which facilitates their use by leaving a wide latitude in the mode of administration (notably by the intravenous route) and in the dose administered without the risk of deleterious side effects.